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Brief Report: Clinical Science

Impact of Hepatitis Coinfection on Healthcare Utilization Among Persons Living With HIV

Crowell, Trevor A. MD*; Berry, Stephen A. MD, PhD*; Fleishman, John A. PhD; LaRue, Richard W. MD, MS*; Korthuis, Philip T. MD, MPH; Nijhawan, Ank E. MD, MPH§; Moore, Richard D. MD*; Gebo, Kelly A. MD, MPH* for the HIV Research Network

Author Information
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 1, 2015 - Volume 68 - Issue 4 - p 425-431
doi: 10.1097/QAI.0000000000000490

Abstract

INTRODUCTION

With the passage of the Patient Protection and Affordable Care Act (ACA), persons living with HIV (PLWH) in the United States can expect healthcare changes that include expansion of insurance coverage, removal of lifetime coverage caps, shifting of resources to community health centers, and incentives to improve care coordination.1 Updated reports of healthcare utilization by PLWH are needed to understand the healthcare needs of this population and plan for changes.

In the United States, 5%–10% of PLWH are coinfected with hepatitis B virus (HBV) and 20%–33% with hepatitis C virus (HCV).2–13 Coinfected patients are at risk for hepatic and extrahepatic complications.13–23 Viral hepatitis has emerged as a leading cause of morbidity and mortality among PLWH.24,25 We hypothesized that healthcare utilization among PLWH might differ according to hepatitis serostatus.

The purpose of this study is to characterize the impact of hepatitis coinfection on utilization of primary HIV care, mental health, and inpatient services in a multisite multistate cohort of PLWH.

METHODS

Site Selection and Data Collection

The HIV Research Network (HIVRN) is a consortium of HIV care sites in 11 US cities. Demographic, laboratory, and treatment data are abstracted from clinical records, deidentified, and consolidated into a uniform database. All sites routinely report primary HIV care visits; 4 also reported mental health and inpatient visits by adult participants from January 1, 2006, through December 31, 2011, and are therefore included in this analysis.

Participants in this analysis were engaged in care during ≥1 year in the study period, as defined by having ≥1 primary HIV care visit, CD4 count, and HIV-1 RNA. The unit of analysis was the patient-year (PY). Institutional review boards at each site and the data coordinating center approved the collection and use of these data for analysis and publication.

Definitions of Variables

Hepatitis serostatus was assessed using HBV surface antigen and HCV antibody. Positive results within 6 months of enrollment and all negative results were carried backward. Results before July 1 were used to categorize hepatitis serostatus from that year onward, whereas results after July 1 were used only for subsequent years. Data were censored at the time of death, loss to follow-up, or end of study.

Clinical and demographic characteristics were assessed using previously published definitions as summarized in Table 1.26 Time-dependent variables included age, CD4, HIV-1 RNA, antiretroviral therapy (ART), and insurance status. Race/ethnicity, gender, and HIV transmission risk factor were categorized by self-report. For secondary analyses, FIB-4 score and use of ART with HBV activity were also considered time-dependent.27

TABLE 1
TABLE 1:
Population Demographic and Clinical Characteristics at Study Entry

Outcomes

Primary HIV care visits were defined as visits to an HIV care provider, not including visits to nurses or subspecialists within multidisciplinary HIV clinics. Mental health visits were visits to a psychologist, psychiatrist, or other mental health provider, not including visits to substance abuse treatment programs such as methadone clinics. Any nonhospice acute care inpatient visit was included. Mortality was assessed by local study staff report.

Data Analysis

Unadjusted healthcare utilization rates were calculated using the total number of visits as the numerator and aggregate person-time as the denominator. Person-time was accrued daily as a fraction of each calendar year, so participants contributed <1 year of observation during the year of enrollment or death.

Number of primary HIV care, mental health, and inpatient visits were modeled using negative binomial regression to estimate incidence rate ratios (IRRs). Age, race/ethnicity, gender, HIV risk factor, CD4, HIV-1 RNA, ART, and insurance status were prespecified covariates of interest. Multivariable models also included categorical indicators for clinical care site to control for site-specific variability and indicators for calendar year to control for secular trends. Several secondary analyses were performed including (1) adding number of primary HIV care visits as a predictor for mental health and inpatient visits; (2) evaluating the effects of FIB-4 score and use of ART with HBV activity (tenofovir, lamivudine, or emtricitabine) among subjects with any hepatitis and with HBV coinfection, respectively; and (3) investigating mortality using logistic regression with variables from the primary models.

To account for multiple observations involving the same individual, all models used generalized estimating equations, clustered on patient, with exchangeable working correlation and robust variance estimators. A 2-sided type I error of 5% was considered statistically significant. All analyses were performed using Stata 12.0 (StataCorp LP, College Station, TX).

RESULTS

Demographic and Clinical Characteristics

A total of 15,927 participants contributed 49,061 person-years of observation time. At study entry, 9146 individuals (57.4%) had HIV monoinfection, 536 (3.4%) HIV/HBV, 2056 (12.9%) HIV/HCV, 115 (0.7%) HIV/HBV/HCV, and 4074 (25.6%) unknown hepatitis serostatus (Table 1). Of those with initially unknown serostatus, 89 participants later contributed person-time to the HIV/HBV coinfected group, 365 HIV/HCV coinfected, and 26 HIV/HBV/HCV tri-infected. The median age ranged from 40.4 (interquartile range: 32.6–47.0) years in the HIV monoinfected group to 47.0 (42.0–51.9) years in the HIV/HCV coinfected group. There were higher proportions of male patients in the HIV/HBV (91.0%) and HIV/HBV/HCV groups (83.5%) than in the other hepatitis serostatus groups. Injection drug use was reported in 5.7% of HIV monoinfected and 6.3% of HIV/HBV coinfected patients but was reported in 60.8% of HIV/HCV and 63.5% of HIV/HBV/HCV patients.

Healthcare Utilization and Serostatus

A total of 227,618 primary HIV care visits, 24,415 mental health visits, and 13,761 inpatient visits were observed. Primary HIV care visit rates were similar across all hepatitis serostatus categories, with an average across time for the full study cohort of 4.64 visits per PY (see Table S1, Supplemental Digital Content http://links.lww.com/QAI/A614). Over the 5-year study period, 23.0% of participants had at least 1 mental health visit, including 21.2% of HIV monoinfected, 21.2% of HIV/HBV coinfected, 34.9% of HIV/HCV coinfected, 30.7% of HIV/HBV/HCV tri-infected, and 18.3% of patients with unknown hepatitis serostatus (see Table S2, Supplemental Digital Content http://links.lww.com/QAI/A614). Among all participants, 33.0% experienced ≥1 inpatient visit during the study period, including 31.6% of those with HIV monoinfection, 37.7% with HIV/HBV coinfection, 46.2% HIV/HCV coinfection, 49.3% HIV/HBV/HCV tri-infection, and 24.6% unknown hepatitis serostatus.

In multivariable analysis, there was no association between hepatitis serostatus and the number of primary HIV care visits (Table 2). Compared with the HIV monoinfected group, patients with HIV/HCV coinfection had significantly higher mental health utilization rates (IRR: 1.27, 95% CI: 1.08 to 1.50). Inpatient utilization was higher in all hepatitis coinfected groups than with HIV monoinfection (HIV/HBV: IRR: 1.23, 95% CI: 1.05 to 1.44, HIV/HCV: IRR: 1.22, 95% CI: 1.10 to 1.36, HIV/HBV/HCV: IRR: 1.31, 95% CI: 1.02 to 1.68). Non-white race/ethnicity was a predictor of decreased mental health utilization as compared with white race/ethnicity. Age >50 years was associated with more primary HIV care visits; age 35–64 years with more mental health visits, and age ≥65 years with more hospitalizations. Private insurance was associated with lower primary HIV care, mental health, and inpatient utilization, as compared with Medicaid, Medicare, and Ryan White/uninsured.

TABLE 2
TABLE 2:
Multivariable Analysis of Risk Factors for Healthcare Utilization

Healthcare Utilization Over Time

Across all hepatitis serostatus groups, primary HIV care visits ranged from 4.5 to 5.5 visits per PY in 2006 and decreased to 4.0 to 4.6 visits per PY in 2011 (unadjusted P for decreasing trend <0.01 for most hepatitis serostatus groups, see Figure S1, Supplemental Digital Content http://links.lww.com/QAI/A614). Mental health utilization decreased from 42.1 to 116.7 visits per 100 PY in 2006 to 21.5 to 67.7 visits per 100 PY in 2011, with significant declines in all hepatitis serostatus groups except unknown. There were statistically significant decreases in unadjusted inpatient utilization across all groups except HIV/HBV/HCV tri-infection and unknown serostatus, from 24.2 to 72.4 visits per 100 PY in 2006 to 19.8 to 34.1 visits per 100 PY in 2011. In multivariable analysis, however, inpatient utilization did not decline across time for the full sample (Table 2) or for any hepatitis serostatus subgroup (see Figure S1, Supplemental Digital Content http://links.lww.com/QAI/A614).

Secondary Analyses

When compared with 1–3 visits per year, increasing primary HIV care utilization was independently associated with increased mental health (4–6 visits per year, IRR: 1.52, 95% CI: 1.41 to 1.64, ≥7 visits per year, IRR: 2.56, 95% CI: 2.34 to 2.80) and inpatient (4–6 visits per year, IRR: 1.22, 95% CI: 1.15 to 1.30, ≥7 visits per year, IRR: 2.43, 95% CI: 2.26 to 2.61) utilization. When controlling for primary HIV care visits, inferences about hepatitis serostatus and healthcare utilization were unchanged.

Among subjects with any hepatitis coinfection, increased FIB-4 score was associated with more primary HIV care visits (FIB-4 ≥3.25, IRR: 1.08, 95% CI: 1.03 to 1.13, as compared with <1.45) and inpatient admissions (IRR: 1.95, 95% CI: 1.76 to 2.16) but no difference in mental health visits (IRR: 0.96, 95% CI: 0.78 to 1.19). Among subjects with HBV coinfection, use of ART with HBV activity was associated with significantly fewer outpatient HIV primary care visits (IRR: 0.83, 95% CI: 0.73 to 0.95) and a trend toward fewer inpatient admissions (IRR: 0.71, 95% CI: 0.48 to 1.05), as compared with the use of ART without HBV activity and after controlling for other covariates. With few observations, the model for mental health utilization did not converge when adjusting for the use of ART with HBV activity.

In multivariable analysis, mortality was higher in all hepatitis coinfected groups than with HIV monoinfection (HIV/HBV: IRR: 1.91, 95% CI: 1.39 to 2.62; HIV/HCV: IRR: 1.30, 95% CI: 1.05 to 1.62; HIV/HBV/HCV: IRR: 2.56, 95% CI: 1.70 to 3.85).

DISCUSSION

Our study makes several important observations about healthcare utilization among PLWH. First, there was no difference in primary HIV care utilization according to hepatitis serostatus. Second, patients with HIV/HCV coinfection demonstrated higher rates of mental health visits than any of the other groups examined. Finally, rates of inpatient utilization were elevated across all hepatitis-infected categories as compared with HIV monoinfection.

Hepatitis coinfection was not associated with increased utilization of primary HIV care. It is possible that PLWH who are coinfected with viral hepatitis have differences in utilization of other subspecialty services, such as gastroenterology or hepatology, but data regarding subspecialty referrals were not available and further investigation is warranted. Decreasing utilization of primary HIV care services over time may be attributable to evolving guideline recommendations for less frequent monitoring for patients with well-controlled HIV disease.28–30

HIV/HCV coinfected participants used more outpatient mental health services than any other hepatitis serostatus group. Prior studies have reported that 3.2%–8.8% of the general US population presents for ≥1 mental health visit per year.31,32 In our study, 12.5%–16.0% of PLWH used mental health services during each calendar year, underscoring the high burden of mental illness among PLWH. As in the general US population, non-white PLWH were less likely to use mental health services than were those self-reporting white race/ethnicity, potentially reflecting cultural barriers to care or other access issues.33 Healthcare delivery systems caring for PLWH must be prepared to handle a high demand for mental health services, particularly among HIV/HCV coinfected patients.

We have previously shown that hepatitis coinfection was associated with increased inpatient utilization during a single year (2010), and here, we demonstrate that this relationship has persisted over time.26 The association between higher FIB-4 score and increased hospitalization rates suggests that hepatocellular dysfunction may directly contribute to the risk of hospitalization in coinfected patients. Use of ART with activity against HBV by persons with HBV coinfection may attenuate the risk of hospitalization.

This study has several potential limitations. First, we relied on HCV antibodies as an indirect marker of HCV coinfection, as HCV RNA levels were not available. However, spontaneous clearance of HCV occurs in less than 10% of PLWH.34 The impact of HCV therapy was not evaluated, but prior studies have reported low treatment rates in the routine care of coinfected PLWH.35–37 Substance abuse is associated with both psychiatric disease and HIV/HCV coinfection, so it is possible that substance abuse contributes to differences in mental health utilization. Treatment of drug addiction was not assessed but may play a particularly important role in the management of HIV/HCV coinfected patients. HIV/HCV coinfected patients tended to be older than patients in other hepatitis serostatus groups. Although all multivariable models included age, residual confounding may have contributed to the differences observed between groups. Lower healthcare utilization among the privately insured raises the possibility that financial differences across groups, such as variable influences of lost work time, may have contributed to some of our observations. Finally, hepatitis serostatus data were not available for all participants, potentially introducing bias if there has been differential failure to capture this information.

Chronic viral hepatitis is associated with differences in mental health and inpatient utilization among PLWH but not primary HIV care visits. Decreases in primary HIV care utilization over time among all PLWH likely reflect shifting treatment paradigms. Third-party payers and policymakers should be aware of the high mental health service utilization by patients with HIV/HCV coinfection and heightened risk of hospitalization among PLWH with any hepatitis coinfection as they design healthcare delivery systems and allocate limited healthcare resources.

ACKNOWLEDGMENTS

HIVRN participating sites: Alameda County Medical Center, Oakland, CA (Howard Edelstein, MD); Children's Hospital of Philadelphia, Philadelphia, PA (Richard Rutstein, MD); Community Health Network, Rochester, NY (Roberto Corales, DO); Drexel University, Philadelphia, PA (Jeffrey Jacobson, MD, Sara Allen, CRNP); Fenway Health, Boston, MA (Stephen Boswell, MD); Johns Hopkins University, Baltimore, MD (Kelly Gebo, MD, Richard Moore, MD, Allison Agwu, MD); Montefiore Medical Group, Bronx, NY (Robert Beil, MD); Montefiore Medical Center, Bronx, NY (Lawrence Hanau, MD); Oregon Health and Science University, Portland, OR (P. Todd Korthuis, MD); Parkland Health and Hospital System, Dallas, TX (Ank Nijhawan, MD, Muhammad Akbar, MD); St. Jude's Children's Hospital and University of Tennessee, Memphis, TN (Aditya Gaur, MD); St. Luke's Roosevelt Hospital Center, New York, NY (Victoria Sharp, MD, Stephen Arpadi, MD); Tampa General Health Care, Tampa, FL (Charurut Somboonwit, MD); University of California, San Diego, CA (W. Christopher Mathews, MD). Sponsoring agencies: Agency for Healthcare Research and Quality, Rockville, MD (Fred Hellinger, PhD, John Fleishman, PhD, Irene Fraser, PhD); Health Resources and Services Administration, Rockville, MD (Robert Mills, PhD, Faye Malitz, MS). Data Coordinating Center: Johns Hopkins University (Richard Moore, MD, Jeanne Keruly, CRNP, Kelly Gebo, MD, Cindy Voss, MA, Nikki Balding, MS).

REFERENCES

1. Martin EG, Schackman BR. What does U.S. health reform mean for HIV clinical care? J Acquir Immune Defic Syndr. 2012;60:72–76.
2. Konopnicki D, Mocroft A, de Wit S, et al.. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS. 2005;19:593–601.
3. Thomas DL, Leoutsakas D, Zabransky T, et al.. Hepatitis C in HIV-infected individuals: cure and control, right now. J Int AIDS Soc. 2011;14:22.
4. Weber R, Sabin C, Reiss P, et al.. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study. Antivir Ther. 2010;15:1077–1086.
5. Thio CL, Seaberg EC, Skolasky R Jr, et al.. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002;360:1921–1926.
6. Arribas JR, Gonzalez-Garcia JJ, Lorenzo A, et al.. Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain. AIDS. 2005;19:1361–1365.
7. Bonacini M, Louie S, Bzowej N, et al.. Survival in patients with HIV infection and viral hepatitis B or C: a cohort study. AIDS. 2004;18:2039–2045.
8. De Luca A, Bugarini R, Lepri AC, et al.. Coinfection with hepatitis viruses and outcome of initial antiretroviral regimens in previously naive HIV-infected subjects. Arch Intern Med. 2002;162:2125–2132.
9. den Brinker M, Wit FW, Wertheim-van Dillen PM, et al.. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS. 2000;14:2895–2902.
10. Kim JH, Psevdos G, Suh J, et al.. Co-infection of hepatitis B and hepatitis C virus in human immunodeficiency virus-infected patients in New York City, United States. World J Gastroenterol. 2008;14:6689–6693.
11. Sollima S, Caramma I, Menzaghi B, et al.. Chronic coinfection with hepatitis B and hepatitis C viruses in an Italian population of HIV-infected patients. J Acquir Immune Defic Syndr. 2007;44:606–607.
12. Lincoln D, Petoumenos K, Dore GJ, et al.. HIV/HBV and HIV/HCV coinfection, and outcomes following highly active antiretroviral therapy. HIV Med. 2003;4:241–249.
13. Castellares C, Barreiro P, Martin-Carbonero L, et al.. Liver cirrhosis in HIV-infected patients: prevalence, aetiology and clinical outcome. J Viral Hepat. 2008;15:165–172.
14. Lee MH, Yang HI, Lu SN, et al.. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a community-based long-term prospective study. J Infect Dis. 2012;206:469–477.
15. Bedimo R, Westfall AO, Mugavero M, et al.. Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients. HIV Med. 2010;11:462–468.
16. Satapathy SK, Lingisetty CS, Williams S. Higher prevalence of chronic kidney disease and shorter renal survival in patients with chronic hepatitis C virus infection. Hepatol Int. 2012;6:369–378.
17. Naing C, Mak JW, Ahmed SI, et al.. Relationship between hepatitis C virus infection and type 2 diabetes mellitus: meta-analysis. World J Gastroenterol. 2012;18:1642–1651.
18. Clifford DB, Evans SR, Yang Y, et al.. The neuropsychological and neurological impact of hepatitis C virus co-infection in HIV-infected subjects. AIDS. 2005;19(Suppl 3):S64–S71.
19. Brau N, Fox RK, Xiao P, et al.. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study. J Hepatol. 2007;47:527–537.
20. Gebo KA, Diener-West M, Moore RD. Hospitalization rates differ by hepatitis C satus in an urban HIV cohort. J Acquir Immune Defic Syndr. 2003;34:165–173.
21. Goedert JJ, Eyster ME, Lederman MM, et al.. End-stage liver disease in persons with hemophilia and transfusion-associated infections. Blood. 2002;100:1584–1589.
22. Puoti M, Torti C, Bruno R, et al.. Natural history of chronic hepatitis B in co-infected patients. J Hepatol. 2006;44(1 suppl):S65–S70.
23. Salmon-Ceron D, Rosenthal E, Lewden C, et al.. Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: the French national Mortalite 2005 study. J Hepatol. 2009;50:736–745.
24. Smith C, Sabin CA, Lundgren JD, et al.. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study. AIDS. 2010;24:1537–1548.
25. Palella FJ Jr, Baker RK, Moorman AC, et al.. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006;43:27–34.
26. Crowell TA, Gebo KA, Balagopal A, et al.. Impact of hepatitis coinfection on hospitalization rates and causes in a multicenter cohort of persons living with HIV. J Acquir Immune Defic Syndr. 2014;65:429–437.
27. Sterling RK, Lissen E, Clumeck N, et al.. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–1325.
28. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. 2013. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed October 28, 2013.
29. Gale HB, Gitterman SR, Hoffman HJ, et al.. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/muL and HIV-1 suppression? Clin Infect Dis. 2013;56:1340–1343.
30. Aberg JA, Gallant JE, Ghanem KG, et al.. Primary care guidelines for the management of persons infected with HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58:e1–e34.
31. Olfson M, Marcus SC. National trends in outpatient psychotherapy. Am J Psychiatry. 2010;167:1456–1463.
32. Wang PS, Lane M, Olfson M, et al.. Twelve-month use of mental health services in the United States: results from the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:629–640.
33. Alegria M, Chatterji P, Wells K, et al.. Disparity in depression treatment among racial and ethnic minority populations in the United States. Psychiatr Serv. 2008;59:1264–1272.
34. Thomas DL, Astemborski J, Rai RM, et al.. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA. 2000;284:450–456.
35. Reiberger T, Obermeier M, Payer BA, et al.. Considerable under-treatment of chronic HCV infection in HIV patients despite acceptable sustained virological response rates in a real-life setting. Antivir Ther. 2011;16:815–824.
36. Scott JD, Wald A, Kitahata M, et al.. Hepatitis C virus is infrequently evaluated and treated in an urban HIV clinic population. AIDS Patient Care STDS. 2009;23:925–929.
37. Vellozzi C, Buchacz K, Baker R, et al.. Treatment of hepatitis C virus (HCV) infection in patients coinfected with HIV in the HIV Outpatient Study (HOPS), 1999-2007. J Viral Hepat. 2011;18:316–324.
Keywords:

HIV; hepatitis B virus; hepatitis C virus; mental health; healthcare utilization; hospitalization

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